Nie Hemin, Lee Lai Yeng, Tong Hui, Wang Chi-Hwa
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576.
J Control Release. 2008 Aug 7;129(3):207-14. doi: 10.1016/j.jconrel.2008.04.018. Epub 2008 Apr 29.
The use of poly(D, L-lactic-co-glycolic acid) for DNA delivery application is limited by its negative surface charge and acidic degradation products. The motivation of the present work was to study the effects of chitosan incorporation into PLGA foams on DNA delivery. PLGA/chitosan composite foams loaded with luciferase plasmid were fabricated by a combination of spray drying and supercritical CO2 foaming techniques. The resultant composite foams showed good morphology and chitosan was found to be poorly crystallized in the PLGA matrixes. The composite foams exhibited a sustained release of DNA (5-9 weeks) with decreasing release rate upon increasing content of chitosan. With this encapsulation technique, it was also observed that the integrity of plasmid was well maintained. Moreover, cell culture results proved that the bioactivity of plasmid released from all foams was well maintained and the incorporation of chitosan in foams helps increase cell adhesion and maintain high cell viability. Therefore, it can be concluded that PLGA/chitosan composite foams fabricated by combining spray drying and supercritical CO2 foaming are promising in DNA delivery applications.
聚(D,L-乳酸-乙醇酸共聚物)在DNA递送应用中的使用受到其负表面电荷和酸性降解产物的限制。本研究的目的是研究壳聚糖掺入PLGA泡沫对DNA递送的影响。通过喷雾干燥和超临界CO2发泡技术相结合制备了负载荧光素酶质粒的PLGA/壳聚糖复合泡沫。所得复合泡沫具有良好的形态,并且发现壳聚糖在PLGA基质中结晶性较差。复合泡沫表现出DNA的持续释放(5-9周),随着壳聚糖含量的增加,释放速率降低。通过这种包封技术,还观察到质粒的完整性得到了很好的维持。此外,细胞培养结果证明,从所有泡沫中释放的质粒的生物活性得到了很好的维持,并且壳聚糖掺入泡沫有助于增加细胞粘附并维持高细胞活力。因此,可以得出结论,通过喷雾干燥和超临界CO2发泡相结合制备的PLGA/壳聚糖复合泡沫在DNA递送应用中具有前景。